ATG4C autophagy related 4C cysteine peptidase [Homo sapiens (human)] - Gene

Summary

Official Symbol: ATG4Cprovided by HGNC
Official Full Name: autophagy related 4C cysteine peptidaseprovided by HGNC
Primary source: HGNC:HGNC:16040
See related: Ensembl:ENSG00000125703 MIM:611339; AllianceGenome:HGNC:16040
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: APG4C; AUTL1; AUTL3; APG4-C; HsAPG4C
Summary: Autophagy is the process by which endogenous proteins and damaged organelles are destroyed intracellularly. Autophagy is postulated to be essential for cell homeostasis and cell remodeling during differentiation, metamorphosis, non-apoptotic cell death, and aging. Reduced levels of autophagy have been described in some malignant tumors, and a role for autophagy in controlling the unregulated cell growth linked to cancer has been proposed. This gene encodes a member of the autophagin protein family. The encoded protein is also designated as a member of the C-54 family of cysteine proteases. Alternate transcriptional splice variants, encoding the same protein, have been characterized. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in brain (RPKM 4.0), placenta (RPKM 3.4) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1p31.3

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (62784132..62865516)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (62662283..62743647)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (63249803..63331187)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

MicroRNA-142-3p inhibits autophagy and promotes intracellular survival of Mycobacterium tuberculosis by targeting ATG16L1 and ATG4c.
Title: MicroRNA-142-3p inhibits autophagy and promotes intracellular survival of Mycobacterium tuberculosis by targeting ATG16L1 and ATG4c.
Epigallocatechin-3-gallate protects cardiomyocytes from hypoxia-reoxygenation damage via raising autophagy related 4C expression.
Title: Epigallocatechin-3-gallate protects cardiomyocytes from hypoxia-reoxygenation damage via raising autophagy related 4C expression.
ATG4 family proteins drive phagophore growth independently of the LC3/GABARAP lipidation system.
Title: ATG4 family proteins drive phagophore growth independently of the LC3/GABARAP lipidation system.
CAV1 and ATG4C serve as useful prognostic biomarkers and candidate therapeutic targets in EOC
Title: Clinicopathological and prognostic significance of caveolin-1 and ATG4C expression in the epithelial ovarian cancer.
Human HAP1 and HeLa cells lacking ATG4B exhibit a severe but incomplete defect in LC3/GABARAP processing and autophagy. By further genetic depletion of ATG4 isoforms using CRISPR-Cas9 and siRNA we uncover that ATG4A, ATG4C and ATGD all contribute to residual priming activity, which is sufficient to enable lipidation of endogenous GABARAPL1 on autophagic structures.
Title: Redundancy of human ATG4 protease isoforms in autophagy and LC3/GABARAP processing revealed in cells.
our results suggested that increased ATG4C expression was associated with worse prognosis in glioma patients. Knockdown of ATG4C suppressed glioma progression by inducing cell cycle arrest and promoting apoptosis of glioma cells possibly through increasing ROS production.
Title: Knockdown ATG4C inhibits gliomas progression and promotes temozolomide chemosensitivity by suppressing autophagic flux.
association between SNPs and Kashin-Beck disease
Title: Genetic association, mRNA and protein expression analysis identify ATG4C as a susceptibility gene for Kashin-Beck disease.
We demonstrate that, in breast cancer cells, ATM and ATG4C are essential drivers of mammosphere formation, suggesting that their targeting may improve current approaches to eradicate breast cancer cells with a stem-like phenotype.
Title: ATM kinase sustains breast cancer stem-like cells by promoting ATG4C expression and autophagy.
miR-376b controls autophagy by directly regulating intracellular levels of two key autophagy proteins, ATG4C and BECN1.
Title: miR-376b controls starvation and mTOR inhibition-related autophagy by targeting ATG4C and BECN1.

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Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genetic Loci Associated with Circulating Levels of Very Long-Chain Saturated Fatty Acids. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of anthropometric traits and evidence of interactions with age and study year in Filipino women. EBI GWAS Catalog EBI GWAS CatalogPubMed
Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Vif	vif	HIV-1 Vif binds more strongly to autophagy-related protein 4 (ATG4)-cleaved form I (LC3-I) than to ATG4-cleaved form II (LC3-II) in an A3G-independent manner	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-31906 (e-PCR)
- UniSTS:5816

D1S2835 (e-PCR), detects polymorphism
- UniSTS:57823

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cysteine-type endopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables cysteine-type endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables cysteine-type peptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-phosphatidylethanolamide deconjugating activity	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in aggrephagy	IBA Inferred from Biological aspect of Ancestor more info
involved_in autophagosome assembly	IBA Inferred from Biological aspect of Ancestor more info
involved_in autophagosome assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in autophagy	IDA Inferred from Direct Assay more info	PubMed
involved_in mitophagy	IBA Inferred from Biological aspect of Ancestor more info
involved_in piecemeal microautophagy of the nucleus	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein delipidation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein processing	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein transport	IEA Inferred from Electronic Annotation more info
involved_in proteolysis	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
is_active_in cellular_component	ND No biological Data available more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: cysteine protease ATG4C

Names: APG4 autophagy 4 homolog C; ATG4 autophagy related 4 homolog C; AUT-like 1, cysteine endopeptidase; AUT-like 3 cysteine endopeptidase; autophagin-3; autophagy-related cysteine endopeptidase 3; autophagy-related protein 4 homolog C; epididymis secretory sperm binding protein

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_032852.4 → NP_116241.2 cysteine protease ATG4C

See identical proteins and their annotated locations for NP_116241.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) is the predominant transcript. Variants 1 and 2 encode the same protein.

Source sequence(s)

AC099794, BC033024, BI518482, BM146035, BQ777265

Consensus CDS

CCDS623.1

UniProtKB/Swiss-Prot

A6NLR8, D3DQ58, Q96DT6, Q96K04

UniProtKB/TrEMBL

A0A384MTY5, Q05D29

Related

ENSP00000322159.4, ENST00000317868.9

Conserved Domains (1) summary

pfam03416
Location:77 → 394

Peptidase_C54; Peptidase family C54
NM_178221.3 → NP_835739.1 cysteine protease ATG4C

See identical proteins and their annotated locations for NP_835739.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses a different splice site in the 5' UTR as compared to variant 1. Variants 1 and 2 encode the same protein.

Source sequence(s)

AC099794, BC008395, BC033024, BM146035, BM720875, BQ777265, DB183325

Consensus CDS

CCDS623.1

UniProtKB/Swiss-Prot

A6NLR8, D3DQ58, Q96DT6, Q96K04

UniProtKB/TrEMBL

A0A384MTY5, Q05D29

Related

ENSP00000360161.3, ENST00000371120.7

Conserved Domains (1) summary

pfam03416
Location:77 → 394

Peptidase_C54; Peptidase family C54